The broad aim of this research is to continue our multi-disciplinary studies on the natural history of bovine leukemia. The significance of this system is based on the exceptional characteristics of the cattle population and on the fact that the bovine leukemia virus (BLV) differs from the other known leukemia viruses in several important properties. Since BLV is usually present in the lymphocytes in a covert or repressed state, a major objective of the proposed research is to develop sensitive molecular and antigen probes for BLV. With these probes and the available methods for the detection of BLV we propose to study the factors that control the expression of the BLV genome, the natural mode of transmission of the virus, and the possibility that BLV may infect and induce leukemia in other animal species. We also plan to apply these probes to further compare BLV with other oncornaviruses. Several sub-populations of lymphocytes have been identified in BLV-infected cattle. We propose to use these populations to investigate the role of immunological factors in the virus-host and tumor-host relationship. Our recent studies indicate that blood-sucking insects play an important role in the horizontal transmission of BLV. Therefore, supplemental money is being requested to convert our existing holding facilities into fly-proof isolation units and to purchase a modular confinement nursery to raise BLV-free animals under strict isolation conditions.